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基于脂质体的药物传递平台的 X 射线辐射触发的基因和药物可控释放。

Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation.

机构信息

ARC Centre of Excellence for Nanoscale Biophotonics, Faculty of Science and Engineering, Macquarie University, North Ryde, 2109, New South Wales, Australia.

The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Kensington, 2052, NSW, Australia.

出版信息

Nat Commun. 2018 Jul 13;9(1):2713. doi: 10.1038/s41467-018-05118-3.

Abstract

Liposomes have been well established as an effective drug delivery system, due to simplicity of their preparation and unique characteristics. However conventional liposomes are unsuitable for the on-demand content release, which limits their therapeutic utility. Here we report X-ray-triggerable liposomes incorporating gold nanoparticles and photosensitizer verteporfin. The 6 MeV X-ray radiation induces verteporfin to produce singlet oxygen, which destabilises the liposomal membrane and causes the release of cargos from the liposomal cavity. This triggering strategy is demonstrated by the efficiency of gene silencing in vitro and increased effectiveness of chemotherapy in vivo. Our work indicates the feasibility of a combinatorial treatment and possible synergistic effects in the course of standard radiotherapy combined with chemotherapy delivered via X-ray-triggered liposomes. Importantly, our X-ray-mediated liposome release strategy offers prospects for deep tissue photodynamic therapy, by removing its depth limitation.

摘要

脂质体作为一种有效的药物递送系统已经得到了很好的证实,这是由于其制备简单和独特的特性。然而,传统的脂质体不适合按需释放内容,这限制了它们的治疗用途。在这里,我们报告了一种结合了金纳米粒子和光敏剂维替泊芬的 X 射线触发脂质体。6 MeV X 射线辐射诱导维替泊芬产生单线态氧,破坏脂质体膜的稳定性,并导致脂质体腔中的货物释放。这种触发策略通过体外基因沉默的效率和体内化疗效果的提高得到了证明。我们的工作表明,在标准放疗联合化疗过程中,通过 X 射线触发脂质体给药,联合治疗具有可行性,并可能产生协同作用。重要的是,我们的 X 射线介导的脂质体释放策略为深部组织光动力疗法提供了前景,消除了其深度限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5274/6045614/888e184fa417/41467_2018_5118_Fig1_HTML.jpg

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